Previous work has shown that bradykinin (BK) interacts with B-2 type receptors in human fibroblasts and initiates a series of biochemical events resulting in increased phospholipase activity, release of arachidonate, and formation of prostaglandins. These prostaglandins, in turn, activate adenyl cyclase and increase cAMP content. The effects of BK on fibroblast cAMP content can be inhibited by the cyclooxygenase inhibitor indomethacin. Several factors alter responsiveness to BK. A number of agents, all of which can increase cAMP by different mechanisms, enhanced effects of BK on both prostaglandin formation and cAMP content. Muscarinic agonists, via interaction with receptors presumably coupled to the guanyl nucleotide-binding protein Ni, also enhanced the effect of BK on prostaglandin formation and cAMP content. Human fibroblasts were also utilized to study the interaction of BK and sodium nitroprusside (SNP). Incubation with SNP markedly increased cGMP content which reached a maximum in less than 30 sec and then declined. BK, which itself only slightly increased cGMP content, dramatically altered the time course of cGMP accumulation in response to SNP; in the presence of both BK and SNP, maximal increases in cGMP content were not attained until 90 sec. SNP, which itself had little or no effect on cAMP content and prostaglandins, enhanced responsiveness to BK. These interactions between SNP and BK were modified by cyclooxygenase products of arachidonate metabolism.